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Comparative Study 2010; 31(5): 657-662 PubMed PMID: 21173747 Citation  Keywords:  Adult, Cells, Cultured, Cytokines:metabolism, Dental Implantation:instrumentation, Dental Implants, Female, Humans, Interferon-gamma:metabolism, Interleukin-1beta:metabolism, Interleukin-4:metabolism, Interleukin-6:metabolism, Lymphocytes:immunology, Male.   

OBJECTIVES: In most of patients in need of implantation treatment in the oral cavity, implants heal well, nevertheless, there are some individuals, in whom titanium implants fail for reasons, which remain unclear.

DESIGN: The aim of our study was to determine if there is a difference between metal influenced IL-1β, IL-4, IL-6, TNF-α and IFN-γ cytokines production in patients with successfully healed implants compared to those, whose implant therapy was unsuccessful.

SETTING: The two study groups included 12 patients with failed dental titanium implants and 9 patients with successfully healed implants. In the subjects, cytokine production was established after lymphocyte cultivation with mercury, nickel and titanium antigens.

RESULTS: IL-1β levels were significantly increased in all patients after stimulation with titanium and in patients with accepted implants compared to patients with failed implants after the stimulation with mercury and titanium. Titanium caused significantly increased IL-6 production in all patients. TNF-α and IFN-γ levels were also significantly increased after the stimulation with titanium. Significantly increased TNF-α levels were found in patients with accepted implants as compared to patients with failed implants.

CONCLUSIONS: Increased production of IL-1β a IL-6 cytokines in reaction to titanium and increased production of TNF-α and IFN-γ cytokines in reaction to mercury, which is very often present in the form of amalgam in the oral cavity of persons in need of implant therapy, can play an important role in immune reactions during implant healing process. In patients with failed titanium implants, decreased production of these cytokines may participate in implant failure....

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Journal Article 2009; 30(1): 131-138 PubMed PMID: 19300393 Citation  Keywords:  Adult, Blood Cells:drug effects, Catechin:pharmacology, Cell Culture Techniques, Cell Nucleus:drug effects, Cell Proliferation:drug effects, Cells, Cultured, Drug Evaluation, Preclinical, Female, Humans, Interleukin-10:blood, Interleukin-6:blood, Interleu.   

OBJECTIVES: Cytokines induce the balance between inflammatory versus regulatory or antibody mediated reactions. So modulating the release of cytokines or inducing them by immunomodulating agents is an attractive mode for treating or help in treating several diseases such as autoimmune diseases. Eriobotrya japonica is a plant that is traditionally thought to have anti-inflammatory activities. Several compounds were isolated from the plant and showed distinctive biological effects. The purpose of this study was to determine the effects of epicatechin (EC) isolated from Eriobotrya Japonica on IL-6, IL-8, and IL-10 productions in whole blood stimulated with phytohemagglutinin (PHA)+lipopolysaccharide (LPS), and to examine if these cytokines are modulated through NFkappaB pathway.

METHODS: Sixteen healthy males and females volunteered in the study. Blood samples were drawn, diluted, and cultured for 24 h with different concentrations of EC and then PHA+LPS was added for another 24 h. The supernatant, then, was harvested and assayed for cytokines. In addition, mixing studies of EC and hydrocortisone were performed to examine the cytoplasmic and nuclear fractions of NFkB levels in association with cytokine production levels.

RESULTS: Increasing concentrations of EC (1-100 microg/ml) in PHA+LPS stimulated whole blood cells culture suppressed significantly (p<0.001) the production of IL-6 and IL-8. Moreover, increasing concentrations of EC modulated significantly the production of IL-10, as there was a significant increase in IL-10 level at 0.1, 1.0, and 10 microg/ml (p=0.058-0.004), while a significant decrease at a concentration of 100 microg/ml EC (p=0.037) was observed. In addition, an additive effect between EC and hydrocortisone (HC, 100 nmol/l) was seen in the production of IL-10, as there was a significant increase in IL-10 level (32%) compared with 27% for EC (10 microg/ml) and 19% HC. Furthermore, a significant decrease in cytoplasmic fractions of NFkappaB p65 level was found in samples containing EC 1, 10 microg/ml, but not in 100 microg/ml, when compared with control (p<0.03). These latter changes were accompanied with a 29%, 67%, and 98% increase, respectively, of NFkappaB p65 in nuclear fractions compared to 24% reduction of NFkappaB p65 level in HC culture (p<0.03).

CONCLUSIONS: These results indicate that EC suppresses the production of pro-inflammatory cytokines, IL6 and IL-8, enhances the production of anti-inflammatory cytokine, IL-10, and stimulates NFkappaB p65 translocation to nucleus in PHA+LPS stimulated whole blood culture....

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Journal Article 2009; 30(6): 733-738 PubMed PMID: 20038922 Citation  Keywords:  Adult, Amniotic Fluid:metabolism, Biomarkers:metabolism, Chorioamnionitis:diagnosis, Female, Fetal Membranes, Premature Rupture:diagnosis, Gestational Age, Humans, Infant, Newborn, Infant, Premature, Interleukin-8:metabolism, Predictive Value of Tests, Pr.   

OBJECTIVE: To determine whether amniotic fluid levels of interleukin-8 (IL-8) are of value in the antenatal diagnosis of acute histological chorioamnionitis (HCA) in preterm premature rupture of membranes (PPROM).

SETTING: Department of Obstetrics and Gynaecology, Charles University, Medical School and University Hradec Kralove, Czech Republic.

METHODS: We compared amniotic fluid IL-8 levels in twenty-nine pregnant women with preterm premature rupture of membranes between 24th and 36th gestational weeks with presence and absence acute histological chorioamnionitis or/and microbial invasion in the amniotic cavity using nonparametric tests (Mann-Whitney test), given the non-normal distribution of analyte. Comparisons of proportions were performed with Shapiro-Wilk normality test.

RESULTS: Patients with HCA had a significantly higher median amniotic fluid IL-8 concentration than patients without the histological signs of chorioamnionitis (1867 pg/mL, 826-5577 versus 1045 pg/mL, 60-4133, p=0.013). Patients with MIAC had a significantly higher median amniotic fluid level than patients without invasion (1888 pg/mL, 519-5577 versus 1225 pg/mL, 60-2766, p= 0.017). Women with HCA and MIAC had a significantly higher median amniotic fluid IL-8 level than women without histological signs of chorioamnionitis and microbial invasion (3117 pg/mL, 826-5577 versus 1468 pg/mL, 394-2766, p=0.034).

CONCLUSIONS: HCA or/and MIAC are associated with a significant increase of amniotic fluid interleukin-8 levels. Amniotic fluid IL-8 seems to be a marker of intraamniotic inflammation....

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Journal Article 2009; 30(4): 535-539 PubMed PMID: 20010489 Citation  Keywords:  Age of Onset, Biomarkers:blood, Fetal Blood, Humans, Infant, Newborn, Infant, Newborn, Diseases:blood, Infection:blood, Interleukin-6:blood, Morbidity, Pneumonia:blood, Prevalence, Sensitivity and Specificity,.   

UNLABELLED: Perinatal infections exert considerably negative effects on morbidity and mortality of newborns.

HYPOTHESIS: elevations of cytokine IL levels may be used as a marker of early-onset neonatal infections.

TARGETS: to establish relationships between elevated IL 6 cytokine levels and neonatal morbidity (cranial and pulmonary).

METHODS: examinations of the umbilical blood for IL 6 values in 392 newborns weighing under 1500 g treated in Ceské Budĕjovice at the Intensive Care Unit and Unit of Intensive Care and Resuscitation.

RESULTS: a statistically significant relationship was demonstrated between elevations of cytokine IL 6 levels and pulmonary morbidity in newborns.

DISCUSSION: the authors recommend examination of cytokine IL levels in the umbilical blood with a possibility to acquire the result within 2 hours after the delivery, which makes neonatologists possible to initiate goal-directed antibiotic therapy....

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Journal Article 2008; 29(3): 303-311 PubMed PMID: 18580842 Citation  Keywords:  Adult, Amniotic Fluid:physiology, Bayes Theorem, Biomarkers, Cesarean Section, Cytokines:blood, Delivery, Obstetric, Female, Fetal Blood:chemistry, Humans, Infant, Newborn, Intercellular Adhesion Molecule-1:blood, Interleukin-6:blood, Interleukin-8:blood,.   

BACKGROUND: Intraamniotic infections negatively affect the mortality and morbidity in parturients and newborns. The prognosis of the disease is associated with a timely diagnosis of these conditions. One of approaches to providing timely information on the risk of the initiation of intra-amniotic infection and early-onset neonatal sepsis is the examination of cytokine levels.

OBJECTIVES: The purpose of the work was to evaluate the importance of the cytokines, IL-6, IL-8, and TNF-alpha, and the adhesive molecule, sICAM-1, as risk factors for early-onset neonatal sepsis and intra-amniotic infections.

METHODS: In a group of 152 women we sampled the blood from the umbilical cord vein immediately after delivery for the determination of the cytokines IL-6, IL-8 and TNF-alpha, and the adhesive molecule, sICAM-1, in newborns.

RESULTS: The sensitivity and specificity results are as follows, respectively: IL-6, 0.800 and 0.972; TNF-alpha, 0.364 and 0.943; IL-8, 0.875 and 0.965; and sICAM-1, 0.833 and 0.952.

CONCLUSIONS: For screening purposes, it is suitable to determine levels of IL-8, IL-6, and sICAM-1. For the screening examination, one of the cytokines mentioned is sufficient, i.e., IL-8 or IL-6, or the level of the adhesive molecule, sICAM-1. It is unnecessary to combine these markers....

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Comparative Study 2008; 29(2): 240-245 PubMed PMID: 18404145 Citation  Keywords:  Adult, Aged, CD4 Lymphocyte Count, CD4-Positive T-Lymphocytes:cytology, Case-Control Studies, Female, Flow Cytometry, Humans, Interleukin-2 Receptor alpha Subunit:metabolism, Male, Middle Aged, Neoplasms:blood, Phenotype, Prognosis, Survival Analysis, T-L.   

AIM: Regulatory T cells (Treg) that prevent autoimmune diseases by suppression of self-reactive T cells may also suppress the immune response against cancer. Experimental tumor models in mice revealed that Tregs are potent inhibitors of an antitumor immune response. The purpose of the study was to identify a CD4+ population of regulatory T cells expressing high levels of CD25(CD4+CD25 high) in the peripheral blood of cancer patients and provide the opportunity to determine whether cancer patients exhibit an expanded CD4+CD25high pool.

METHODS: The frequency of CD4+CD25high in the peripheral blood of 62 cancer patients and 15 healthy donors was determined by flow cytometry.

RESULTS: Compared with healthy donors, cancer patients have an increasing prevalence of CD4+CD25high T cells in the peripheral blood with characteristics of Tregs, i.e. they are CD45-RA(), CD69(-). Among patients, those with higher percentages of CD4+CD25high T cells had a poor prognosis than did those with lower percentages.

CONCLUSION: We provide evidence of an increased pool of CD4+CD25high in the peripheral blood of cancer patients, which may be related to immunosuppression and tumor progress in cancer patients. This finding suggests that the use of immunomodulatory therapy to treat cancer patients may be an effective strategy....

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Journal Article 2008; 29(1): 75-79 PubMed PMID: 18283248 Citation  Keywords:  Aged, Aged, 80 and over, Alzheimer Disease:blood, Amyloid beta-Peptides:blood, Biomarkers:blood, Case-Control Studies, Female, Humans, Interleukin-10:blood, Interleukin-6:blood, Middle Aged, Tumor Necrosis Factor-alpha:blood,.   

: Alzheimer's disease (AD) belongs to a group of neurodegenerative disorders. It is characterized by irreversible and progressive memory loss accompanied with decline in other cognitive functions. At a microscopic level, the typical neuropathologic features, senile plaques and neurofibrillary lesions are found. The pathological processes lead to neuronal loss, synaptic dysfunction and inappropriate activity of neurotransmitters. The major constituent of senile plaques is abnormally aggregated beta amyloid protein. Beta amyloid (Abeta) is a short (40-42 amino acid) product of proteolysis of the transmembrane amyloid precursor protein (APP). Extracellular depositions of Abeta 1-42 may initiate a wide range of pathological processes including glia activation, neuroinflammation and neuronal apoptosis. There is convincing evidence that inflammatory response to accumulation of beta amyloid plays a pivotal role in the progression of neuropathological changes found in AD. Current research was directed at assessing beta amyloid, cytokines (IL-6, IL-10 and TNF alpha) plasma levels in women with AD. Hundred and twenty four women, aged between 59 to 86 years, were enrolled in the study. Amongst them 57 were diagnosed with AD (29 subjects in early stage and 28 subjects with moderate to severe stadium of disease) and 67 women without dementia were investigated as a control group. The lowest values of Abeta 1-42 were found in AD subjects in moderate to severe stage of disease as compared with the early stage of AD (p< 0.05) and the control group (p<0.01). Change in IL-6 values was significantly different between groups with the lowest values found in women without dementia. Both subset of AD patients demonstrated statistically enhanced IL-6 levels when compared with the control group (p<0.001, p<0.01 respectively for early and moderate/severe stage of AD). Moreover, our study revealed a trend to increase in TNF alfa and IL-10 values in AD. However, those differences were not statistically significant. In addition, we did not detect any correlations between plasma beta amyloid and investigated cytokines....

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Journal Article 2007; 28(4): 422-426 PubMed PMID: 17693974 Citation  Keywords:  Adolescent, Anorexia Nervosa:immunology, Antibodies:immunology, Antigens, CD28:immunology, Antigens, CD3:immunology, CD4-Positive T-Lymphocytes:metabolism, Calcium:metabolism, Case-Control Studies, Child, Female, Humans, Interleukin-2:metabolism, Lymphocy.   

OBJECTIVES: Anorexia nervosa (AN), a disease of chronic human starvation has a deep impact on the function of several organ systems. We hypothesized that disturbed cellular activation may contribute to complications in AN. We tested our assumption on short-term activation kinetics of lymphocytes.

PATIENTS AND METHODS: Blood was taken from 11 AN and 10 healthy adolescents. Peripheral blood mononuclear cells were isolated and CD4+ lymphocytes were then activated with phythohemagglutinin for the determination of calcium-influx and membrane potential. Moreover, cells were also activated by anti-CD3/anti-CD28 coated beads and three days after the prevalence of interleukin-2 positive CD4+ cells were determined.

RESULTS: After activation, more time was required to reach maximal calcium content in CD4+ cells of AN patients than in those of controls (control vs. AN (median, range): 86 [45-232] vs. 215 [59-235] second, p<0.05), but the rate of membrane potential alteration was similar. The number of interleukin 2 positive CD4+ cells was lower in AN (11.50 [7.60-15.30] vs. 13.50 [12.00-22.00] %, p<0.05). No association was detected between cell activation and any of clinical or anthropometric data of AN patients.

CONCLUSIONS: These results suggest that AN may have an impact on calcium handling of the cells and, hence, cell activation characteristics. We assume that altered calcium flux kinetics may contribute to complications present in AN....

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